With the molecular identification of tumor specific antigens, a number of cancer vaccine trials targeting these antigens in the form of synthetic peptide epitopes have been attempted. Specific immune responses were observed in some clinical trials, however, only a minority of treated patients experienced clinical responses. Because of the weak clinical effectiveness of current cancer vaccine trials, many investigators are trying to discover more immunogenic antigens, new effective adjuvants, formulations, vectors or vaccination methods (Jager, E., et al., Int. J. Cancer. 106:817-20, 2003; Belardelli, F., et al., Cancer Res. 64:6827-30, 2004; Rosenberg, S. A., et al., Nat. Med. 10:909-15, 2004). Another obstacle for cancer vaccine trials is that patient enrollment is often limited by the indispensable requirement for antigen expression in cancer cells. Most attractive tumor specific antigens discovered so far have only a limited expression frequency in cancer, thus preventing many patients to meet adequate eligibility criteria.
NY-ESO-1 is a germ cell protein that is often expressed by cancer cells, but not normal somatic cells (Chen, Y. T. et al., Proc. Natl. Acad. Sci. USA. 94:1914-8, 1997). It was discovered by serological identification of antigens by recombinant expression cloning (SEREX) using the serum of an esophageal cancer patient (Chen, Y. T. et al., Proc. Natl. Acad. Sci. USA. 94:1914-8, 1997; Sahin, U. et al., Proc. Natl. Acad. Sci. USA. 92:11810-3, 1995). The frequent finding of humoral and cellular immune responses against this antigen in cancer patients with NY-ESO-1 expressing tumors makes it one of the most immunogenic human tumor antigens (Jager, E. et al., J. Exp. Med. 187:265-70, 1998). However, the frequency of NY-ESO-1 expression in melanoma, lung, breast, ovarian, and bladder cancers is only 20-30% and often heterogeneous (Chen, Y. T. et al., Proc. Natl. Acad. Sci. USA. 94: 1914-8, 1997; Jungbluth, A. A. et al., Int. J. Cancer. 92:856-60, 2001).
Although advances in the treatment of cancer have been made, there still exists a need for improved methods of treating cancer. In particular, there exists a need for improved cancer vaccines that can be used therapeutically and/or prophylactically.